The present invention relates to a method of the production of analgesia in humans and other warm-blooded animals in need of such therapy which comprises administering an amount effective to produce analgesia of Substance P or an analog thereof which contains the essential amino acid sequence of Substance P, and to pharmaceutical preparations adapted for the administration of said compounds.
Substance P is a polypeptide of mammalian origin discovered by Von Euler and Gaddum, J. Physiol. 72, 74 (1931) in extracts of equine brain and intestinal tissue; it was subsequently isolated from cattle brain by Zuber and Jaques, Angew. Chemie (Int. Ed.) 1, 160 (1962). It is known to be a sensory-transmitter substance and a mediator in inhibitory processes.
The amino acid sequence of Substance P is H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH.sub.2.
Substance P was isolated from bovine hypothalamus by Chang and Leeman, J. Biol. Chem. 245, 4784 (1970), who observed that the crude substance was sialogogic, i.e. it stimulated salivary secretion when injected into anaesthetized rats. The purified substance exhibited similar activity, and was found to exert an effect on smooth muscle and to lower blood pressure and to act as a vasodilator in mammals.
Substance P has been synthesized and is commercially available. Its synthesis is disclosed in Leeman et al. U.S. Pat. No. 3,912,711. The preparation of various analogs of Substance P is described in Scandrett U.S. Pat. No. 3,862,114.
Substance P is known to affect the mammalian central nervous system, but its observed pharmacological action has been confined to its sialogogic and hypotensive activity, and its property of producing intestinal contractions.